- Title
- A critical role for donor-derived IL-22 in cutaneous chronic GVHD
- Creator
- Gartlan, Kate H.; Bommiasamy, Hemamalini; Kuns, Rachel D.; Chang, Karshing; Fedoriw, Yuri; Shea, Thomas; Coghill, James; Zaiken, Michael; Plank, Maximillian W.; Foster, Paul S.; Clouston, Andrew D.; Blazar, Bruce R.; Paz, Katelyn; Serody, JS; Hill, GR; Wilkinson, Andrew N.; Owen, Mary; Reichenbach, Dawn K.; Banovic, Tatjana; Wehner, Kimberly; Buchanan, Faith; Varelias, Antiopi
- Relation
- American Journal of Transplantation Vol. 18, Issue 4, p. 810-820
- Publisher Link
- http://dx.doi.org/10.1111/ajt.14513
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2018
- Description
- Graft-versus-host disease (GVHD) is the major cause of nonrelapse morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Prevention and treatment of GVHD remain inadequate and commonly lead to end-organ dysfunction and opportunistic infection. The role of interleukin (IL)-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T cell–derived IL-22 significantly exacerbates cutaneous chronic GVHD and that IL-22 is produced by highly inflammatory donor CD4+ T cells posttransplantation. IL-22 and IL-17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL-22+ Th17 cells. Donor Th22 and IL-22+ Th17 cells share a similar IL-6–dependent developmental pathway, and while Th22 cells arise independently of the IL-22+Th17 lineage, IL-17 signaling to donor Th22 directly promotes their development in allo-SCT. Importantly, while both IL-22 and IL-17 mediate skin GVHD, Th17-induced chronic GVHD can be attenuated by IL-22 inhibition in preclinical systems. In the clinic, high levels of both IL-17A and IL-22 expression are present in the skin of patients with GVHD after allo-SCT. Together, these data demonstrate a key role for donor-derived IL-22 in patients with chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation.
- Subject
- basic (laboratory) research/science; bone marrow/hematopoietic stem cell transplantation; bronchiolitis obliterans (BOS); cytokines/cytokine receptors; graft-versus-host disease (GVHD); immunobiology
- Identifier
- http://hdl.handle.net/1959.13/1446292
- Identifier
- uon:42824
- Identifier
- ISSN:1600-6135
- Language
- eng
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